Extracellular signal-regulated kinase 1/2 plays a pro-life role in experimental brain stem death via MAPK signal-interacting kinase at rostral ventrolateral medulla

Deuchars, Susan A., K. Michael Spyer, and Michael P. Gilbey. Stimulation within the rostral ventrolateral medulla can evoke monosynaptic GABAergic IPSPs in sympathetic preganglionic neurons in vitro. J. Neurophysiol. 77: 229–235, 1997. The inhibitory responses of identified sympathetic preganglionic neurons (SPNs) to stimulation within the rostral ventrolateral medulla (RVLM) were studied to determine their nature and pharmacology. Whole cell patch-clamp recordings were made from 36 SPNs in the upper thoracic segments of the spinal cord in a neonatal rat brain stem-spinal cord preparation. Neurons were identified as SPNs on the basis of their antidromic activation after stimulation of the ipsilateral segmental ventral root and their morphology and location in the intermediolateral cell column and intercalated nucleus. In all SPNs, electrical stimulation of the RVLM evoked fast excitatory postsynaptic potentials (EPSPs) that were mediated by non- N-methyl-d-aspartate (NMDA) and NMDA receptors. These excitatory responses were the most prominent response in control artificial cerebrospinal fluid and have been studied previously. In 22 of the SPNs, RVLM stimulation also elicited fast inhibitory postsynaptic potentials (IPSPs), which increased in amplitude as the membrane was depolarized. Five of these neurons were not studied further as they responded occasionally with IPSPs that had highly variable onset latencies indicating the involvement of a polysynaptic pathway. In the remaining SPNs ( n = 17), the evoked IPSPs persisted in the presence of the excitatory amino acid antagonists 6-cyano-7-nitroquinoxaline-2,3,-dione and d,l-2-amino-5-phosphonopentanoic acid. In eight of these SPNs, it was necessary to block the EPSPs to reveal the IPSPs. In the 7 SPNs tested, the onset latencies of the IPSPs were not significantly different from the onset latencies of the fast EPSPs. The low sweep-to-sweep fluctuations in onset latency of individual IPSPs (absolute average deviation: 0.4 ms) indicated that the IPSPs were elicited by activation of a monosynaptic pathway. The amplitudes of the IPSPs decreased in amplitude as the membrane was hyperpolarized and reversed in polarity at −70.3 ± 1.7 mV (mean ± SD), which was close to the equilibrium potential for chloride ions. In addition, in seven SPNs, bath applications of 5 μM bicuculline, a γ-aminobuturic acid-A (GABAA) antagonist, abolished or reduced the evoked IPSPs. Five SPNs also were studied that displayed ongoing IPSPs. The amplitudes of these IPSPs increased with membrane depolarization and were blocked by bath applications of 5 μM bicuculline, suggesting that they also were mediated by activation of GABAA receptors. These results demonstrate the existence of a bulbospinal GABAergic pathway impinging directly onto SPNs. This pathway may be tonically active in the neonatal rat brain stem-spinal cord preparation.

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Heme oxygenase-1 plays a pro-life role in experimental brain stem death via nitric oxide synthase I/protein kinase G signaling at rostral ventrolateral medulla

Journal of Biomedical Science ◽

10.1186/1423-0127-17-72 ◽

2010 ◽

Vol 17 (1) ◽

pp. 72 ◽

Cited By ~ 7

Author(s):

Kuang-Yu Dai ◽

Samuel HH Chan ◽

Alice YW Chang

Keyword(s):

Nitric Oxide ◽

Protein Kinase ◽

Nitric Oxide Synthase ◽

Brain Stem ◽

Heme Oxygenase ◽

Rostral Ventrolateral Medulla ◽

Protein Kinase G ◽

Ventrolateral Medulla ◽

Heme Oxygenase 1 ◽

Oxide Synthase

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Brain stem activity changes associated with restored sympathetic drive following CPAP treatment in OSA subjects: a longitudinal investigation

Journal of Neurophysiology ◽

10.1152/jn.00092.2015 ◽

2015 ◽

Vol 114 (2) ◽

pp. 893-901 ◽

Cited By ~ 14

Author(s):

Linda C. Lundblad ◽

Rania H. Fatouleh ◽

David K. McKenzie ◽

Vaughan G. Macefield ◽

Luke A. Henderson

Keyword(s):

Brain Stem ◽

Signal Intensity ◽

Rostral Ventrolateral Medulla ◽

Ventrolateral Medulla ◽

Bold Signal ◽

Functional Changes ◽

Cpap Treatment ◽

Obstructive Sleep ◽

Medullary Raphe ◽

The Brain

Obstructive sleep apnea (OSA) is associated with significantly elevated muscle sympathetic nerve activity (MSNA), leading to hypertension and increased cardiovascular morbidity. Although little is known about the mechanisms responsible for the sympathoexcitation, we have recently shown that the elevated MSNA in OSA is associated with altered neural processing in various brain stem sites, including the dorsolateral pons, rostral ventrolateral medulla, medullary raphe, and midbrain. Given the risk associated with elevated MSNA, we aimed to determine if treatment of OSA with continuous positive airway pressure (CPAP) would reduce the elevated MSNA and reverse the brain stem functional changes associated with the elevated MSNA. We performed concurrent recordings of MSNA and blood oxygen level-dependent (BOLD) signal intensity of the brain stem, using high-resolution functional magnetic resonance imaging, in 15 controls and 13 subjects with OSA, before and after 6 mo CPAP treatment. As expected, 6 mo of CPAP treatment significantly reduced MSNA in subjects with OSA, from 54 ± 4 to 23 ± 3 bursts/min and from 77 ± 7 to 36 ± 3 bursts/100 heart beats. Importantly, we found that MSNA-coupled changes in BOLD signal intensity within the dorsolateral pons, medullary raphe, and rostral ventrolateral medulla returned to control levels. That is, CPAP treatment completely reversed brain stem functional changes associated with elevated MSNA in untreated OSA subjects. These data highlight the effectiveness of CPAP treatment in reducing one of the most significant health issues associated with OSA, that is, elevated MSNA and its associated elevated morbidity.

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Responses of neurons in the rostral ventrolateral medulla to whole body rotations: comparisons in decerebrate and conscious cats

Journal of Applied Physiology ◽

10.1152/japplphysiol.00180.2011 ◽

2011 ◽

Vol 110 (6) ◽

pp. 1699-1707 ◽

Cited By ~ 28

Author(s):

V. J. DeStefino ◽

D. A. Reighard ◽

Y. Sugiyama ◽

T. Suzuki ◽

L. A. Cotter ◽

...

Keyword(s):

Brain Stem ◽

Body Position ◽

Rostral Ventrolateral Medulla ◽

Whole Body ◽

Ventrolateral Medulla ◽

Otolith Organs ◽

Decerebrate Cats ◽

Conscious Animals ◽

The Brain ◽

Stimulation Of

The responses to vestibular stimulation of brain stem neurons that regulate sympathetic outflow and blood flow have been studied extensively in decerebrate preparations, but not in conscious animals. In the present study, we compared the responses of neurons in the rostral ventrolateral medulla (RVLM), a principal region of the brain stem involved in the regulation of blood pressure, to whole body rotations of conscious and decerebrate cats. In both preparations, RVLM neurons exhibited similar levels of spontaneous activity (median of ∼17 spikes/s). The firing of about half of the RVLM neurons recorded in decerebrate cats was modulated by rotations; these cells were activated by vertical tilts in a variety of directions, with response characteristics suggesting that their labyrinthine inputs originated in otolith organs. The activity of over one-third of RVLM neurons in decerebrate animals was altered by stimulation of baroreceptors; RVLM units with and without baroreceptor signals had similar responses to rotations. In contrast, only 6% of RVLM neurons studied in conscious cats exhibited cardiac-related activity, and the firing of just 1% of the cells was modulated by rotations. These data suggest that the brain stem circuitry mediating vestibulosympathetic reflexes is highly sensitive to changes in body position in space but that the responses to vestibular stimuli of neurons in the pathway are suppressed by higher brain centers in conscious animals. The findings also raise the possibility that autonomic responses to a variety of inputs, including those from the inner ear, could be gated according to behavioral context and attenuated when they are not necessary.

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